The interaction of 18 strains of Leptospira (2 species, 9 serovars) and a strain of Leptonema illini with 6 tissue cultured cell lines (3 epithelial and 3 fibroblastic) during leptospiral replication was investigated. Cytopathic effects ware observed not only on fibrablastic cells but also on epothelial cells infected with leptospires. In addition to most strains of Leptospira interrogans, Leptospira biflexa and L. illini produced cytopathic effects. Thus the cytopathic effect caused by leptospires of L. interrogans servar icterofaemoeehagiae atrain RGA produced cytopathic effect without entering the cells. On the other hand, strain Pyrogenes of L.. Interrogans serovar pyrogenes and strain Akiyami A of serovar autumnalis efficiently attached to and entered pyrogenes and strain Akiyami A of serovar autumnalis efficiently attached to and entered Sf1Ep cells, although they did not produce any cytopathic effect. These results suggest that the cytopathic effects of some pathogenic leptospires are caused by extracellular toxic substances produced by the microorganisms.